Uganda, like much of sub-Saharan Africa, is in the midst of a public health crisis. Numerous highly infectious diseases outbreaks have occurred in very quick succession over the past few years. This implies the need for precise and effective targeting of resources, where laboratory disease detection, identification, monitoring, risk mapping and assessment systems are put in place as the best strategy to stop their spread at an early stage, or prevent them altogether. The proposal describes a multiyear project for investigating and controlling vector-borne and zoonotic disease in Uganda. The research will focus on the following specific goals: a) assessing the disease burden caused by vector-borne and zoonotic diseases in Uganda; b) describing the enzootic, epizootic and epidemic parameters associated with vector-borne and zoonotic diseases in Uganda; c) building laboratory capacity to detect vector-borne and zoonotic pathogens; d) reducing morbidity and mortality due to vector-borne and zoonotic diseases in Uganda; e) characterizing the reservoir hosts and vectors of vector-borne and zoonotic diseases in Uganda; f) acquiring a diverse archive collection of bacterial and viral isolates from Uganda; and g) developing and evaluating economically sustainable control strategies under field conditions. The study proposal has four study sections each with varied aims and activities as follows: 1. Plague studies: aim to reduce morbidity and mortality by designing, evaluating and disseminating economically sustainable plague control strategies based on scientific knowledge gained from investigating the host, vector and pathogen epidemiology and ecology,the associated environmental and human behavioral risk factors, accurate and laboratorybased case surveillance and confirmation, pathogen microbiology and clinical treatment. The program will conduct a series of field and laboratory based epidemiological and ecological investigations on human and animal plague in the disease endemic West Nile region of Uganda characterizing plague causative agents, the vectors (fleas) as well as the reservoir host populations; evaluate and disseminate innovative yet economically sustainable local strategies for effective control of plague bacteria and fleas; evaluate rapid diagnostic testing methods that will allow rapid field based detection of human plague for effective case management; evaluate efficacy of drugs for effective cheaper treatment of human plague; strengthen the capacity of local laboratory facilities and human resource; disseminate evidence based scientific research data to promote, enhance and advance translation of significant research findings into public health policies and practices; and conduct other innovative studies geared towards safeguarding public. 2. Arboviruses studies: aim to improve and maintain an effective, coordinated program of diagnostics and surveillance of vector-borne viral infections to collect data and information on arboviruses, vectors and reservoir systems, ensuring prompt recognition, and confirmation of arboviruses disease outbreaks. The proposal includes two studies: A repeated cross-sectional field study of at multiple locations around Uganda will identify vectors and agents present at these locations at particular times of the year to get a better understanding of the interactions between mosquitoes, arboviruses, animal hosts and environmental factors. The other part of the study will make collections of mosquitoes, ticks, rodents and bats from as many varied sites, aiming at sites where there is an interface with the wild animals and humans in the diverse ecosystem of Uganda. Surveillance arbovirus activity in humans will also be conducted from sentinel centers in different regions of the country. 3. High Hazard Hemorrhagic Fever Viruses: aim to investigate, characterize and control environmental and faunal aspects of filovirus outbreaks in Uganda and neighboring countries including 1) identifying those reservoirs which support the maintenance of filoviruses in nature, 2) determining the environmental factors which facilitate their spread, 3) strengthening of the capability within Uganda to more rapidly detect hemorrhagic fever outbreaks, and 4) developing better educational materials to enhance hemorrhagic fever awareness among the population. The project will offer the opportunity to continue providing first line diagnostic testing for suspct hemorrhagic fevers and to continue validating these existing assays on a variety of field specimens. In addition it will offer the opportunity to rapidly develop modifications to protocols and procedures as needed to maintain the high level of quality for detection and surveillance. Comprehensive ecological studies will be conducted in regions where filovirus outbreaks have recently occurred to further investigate the zoonotic origins of these outbreaks and to define the natural reservoir of Ebola virus and determine potential route(s) of virus transmission 4. Acute Febrile Illnesses case based surveillance: aims to develop and implement a national sentinel surveillance system for case-based surveillance for zoonotic diseases and AFIcausing diseases throughout Uganda, with a focus on trans-boundary regions. The aim is to support Uganda towards achieving self-sufficiency by consolidating ongoing surveillance programs to lead to the development of a nationally-based surveillance system that will aid in recognizing and responding to health-related events. This national sentinel surveillance system will be based on a hub-and-spoke model, with the existing referral hospitals serving as hubs centered in regions throughout the nation, and the spokes reaching out to HC Level IV facilities in surrounding districts. Each hub will provide services and expertise in public health, epidemiology, and laboratory science. This project will benefit the people of Uganda by improving the surveillance system for vectorborne and zoonotic diseases, thereby reducing the morbidity and mortality associated with these diseases, investing in the health infrastructure of Uganda, educating and training public health officials and the public on surveillance and control of these diseases, investing in academic development and capacity building for Ugandan Research Institutions, Universities and the Ministry of Health. Additionally, this project will benefit our partner, the USCDC by addressing the Healthy People 2010 priority area(s) of Immunization and Infectious Diseases and is in alignment with NCEZID performance goal(s) to protect Americans from infectious diseases and also in alignment with the CDC Framework for Preventing Infectious Diseases: Sustaining the Essentials and Innovating for the Future-CDC's ID Framework (2011). Funding of US $ 2,137,897.21 is requested to enable carrying out the proposed activities.